Parkinson disease (PD) is a degenerative disorder of the central nervous system. The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain. Degeneration of the nigrostriatal pathway causes reduction in the striatal concentration of dopamine. Dopamine is a neurotransmitter or chemical messenger in the body which affects brain processes controlling movement, balance, walking, emotional response, and ability to experience pleasure and pain. The major striatal targets of dopaminergic innervation reside in the medium spiny neurons (MSNs) of the striatopallidal (indirect) and striatonigral (direct) output pathways. The MSNs of the direct output pathway express D1 dopamine receptors whereas those in the indirect pathway express D2 receptors. Currently, there is no cure for Parkinson's disease, but drugs can relieve at least some of the symptoms. Modem treatments are effective at managing the early motor symptoms of the disease, mainly through the use of levodopa. About 75% of Parkinson's disease patients are treated with levodopa, a prodrug for dopamine discovered over 50 years ago (Dopamine Replacement Therapy).
Levodopa has common serious side effects including induced dyskinesia (LID), impulsive control disorders (ICD), psychotic symptoms and sleep disturbances. LID is progressive (90% of PD patients develop LID within 10 yrs). Accordingly there is a need for new treatments that are effective in treating PD. The present invention can fulfill this and related needs.